Variant rs4963051 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.6855G>A(p.Thr2285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,602,934 control chromosomes in the GnomAD database, including 24,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2030 hom., cov: 30)

Exomes 𝑓: 0.17 ( 22961 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.76

Variant links:

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B links:

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-1243735-G-A is Benign according to our data. Variant chr11-1243735-G-A is described in ClinVar as [Benign]. Clinvar id is 403142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.6855G>A	p.Thr2285=	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.57-1097C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.6855G>A	p.Thr2285=	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.57-1097C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24270

AN:

151428

Hom.:

2028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.00502

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.146

AC:

36308

AN:

248502

Hom.:

3184

AF XY:

0.151

AC XY:

20356

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0814

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.00317

Gnomad SAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.170

AC:

246445

AN:

1451388

Hom.:

22961

Cov.:

146

AF XY:

0.170

AC XY:

122542

AN XY:

722370

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.0857

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.00209

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.160

AC:

24282

AN:

151546

Hom.:

2030

Cov.:

AF XY:

0.159

AC XY:

11773

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.00503

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.169

Hom.:

717

Bravo

AF:

0.151

EpiCase

AF:

0.172

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over